Antiepileptic medication in pregnancy: late effects on the children's central nervous system development

Although research results suggest that antiepileptic medication is teratogenic (causes birth defects), in practice it is difficult to separate drug effects from effects due to maternal seizures themselves or to social and economic risk factors, also elevated among epileptic women. A study was carried out to disentangle these effects, using 61 children selected from a larger sample born to 132 epileptic mothers. None of these women had seizures during the pregnancy. The mothers had taken phenobarbital only (13 subjects); carbamazepine only (12); both drugs (12); or no antiepileptic drugs at all (24) during pregnancy; a matched control group was also selected. The study was long-term; the current report concerns 57 children between the ages of 6 and 13. The children underwent neurologic examination (and were scored as either normal, presence of minor neurologic dysfunctions, or abnormal); testing for reading, spelling, and arithmetic; and behavioral evaluation. Results showed no differences between the children of epileptic mothers and controls in the rate of minor neurologic dysfunction. However, the group born to mothers from the phenobarbital-only group had a higher proportion of poor performers on the arithmetic and spelling tests. No differences were found for other measures of cognitive development or behavior. Physical measurements revealed normal weight and height for all children, but skull circumferences for phenobarbital-only children were smaller (this may be linked to an adverse effect on cognitive development). A greater proportion of the children of epileptic mothers (including those whose mothers had not taken an antiepileptic drug) than controls had minor physical abnormalities (abnormality of posture, muscle tone, or coordination). Thus both major and minor birth defects seem to be associated more closely with the maternal epilepsy than the medication taken during pregnancy. But the results also suggest that phenobarbital may be a potential teratogen; the issue deserves further investigation. (Consumer Summary produced by Reliance Medical Information, Inc.)